Acetic Acid → Ethyl 4-[(4-cyano-4-pyridin-2-ylpiperidin-1-yl)methyl]-1-oxo-1,8a-dihydronaphthalene-2-carboxylate
Reaction equation
[CH:1]([C:3]1[CH:4]=[C:5]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:6](=[O:13])N2[C:12]=1[CH:11]=[CH:10][CH:9]=[CH:8]2)=O.[N:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[C:25]1([C:31]#[N:32])[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1.[C:33](O)(=O)C.ClC(Cl)C.C([BH3-])#N>>[C:31]([C:25]1([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][N:19]=2)[CH2:26][CH2:27][N:28]([CH2:1][C:3]2[CH:4]=[C:5]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:6](=[O:13])[CH:33]3[C:12]=2[CH:11]=[CH:10][CH:9]=[CH:8]3)[CH2:29][CH2:30]1)#[N:32]Participants
Reactant 5
Product 1
Conditions
- Temperature
- 120 °C
Procedure
In a 10-20 mL Emrys™ process vial, a mixture of the ethyl 1-formyl-4-oxo-4H-quinolizine-3-carboxylate (684 mg, 2.79 mmol), 4-pyridin-2-ylpiperidine-4-carbonitrile (627 mg, 3.35 mmol), glacial acetic acid (0.96 mL, 16.7 mmol) and 4.1 mL of dichloroethane was stirred vigorously. To the stirring mixture was added resin-bound MP-cyanoborohydride (2.74 g, 5.58 mmol). The mixture was heated via Emrys Optimizer™ microwave to 120° C. for 30 minutes. Filtration and solvent removal provided material, which was subjected to silica gel chromatography eluting with 55-75% EtOAc in hexanes. Collection of product containing fractions and removal of solvent afforded the ethyl 4-[(4-cyano-4-pyridin-2-ylpiperidin-1-yl)methyl]-1-oxo-1,8a-dihydronaphthalene-2-carboxylate.
Workup
- filtrationFiltration and solvent removal
- customprovided material, which
- washeluting with 55-75% EtOAc in hexanes
- customCollection of product
- additioncontaining
- customfractions and removal of solvent
Sources & evidence
- ORD record
- ord-5500064f15304e10bfb6bd26941da0e6
- Source dataset
- uspto-grants-2012_09
- Patent number
- US08258135B2
Reaction notes
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